The purpose of the proposed research is to provide information about the structure and specific functions of the various cell types within normal and malignant mammary glands. (1) Mammary tissues from experimental animals (including preneoplastic lesions, hormone-dependent tumors and hormone-independent tumors) will be studied in vivo and in vitro. The fine structure and function of the different cell populations within these tissues will be elucidated, and some cellular responses to specific hormones will be characterized. (2) Human breast tissue will be maintained in organ culture and examined after exposure to specific hormones. Electron microscopy and electron microscopic autoradiography will be employed to characterize the cell types and to examine certain functional alterations that occur in the tissue (e.g., the ability of cells to divide, incorporate amino acids and bind hormones). (3) The ability of preneoplastic and neoplastic mammary tissues to elicit the ingrowth of new capillaries (a process known as mammary tumor angiogenesis) will be evaluated, and the relationship of this process to malignant transformation will be studied in hormone-dependent and hormone-independent mammary tumors. The role of hormonal regulation in tumor angiogenesis has not been studied heretofore; positive results could lead to new therapeutic methods for controlling the growth of human malignancies.